title: Molecular epidemiology and interferon susceptibility of the natural recombinant hepatitis C virus strain RF1_2k/1b.
abstract: BACKGROUND
  Hepatitis C virus (HCV) genotype is an important determinant of virological response to antiviral therapies. Currently, there are no data available on the molecular epidemiology and interferon susceptibility of the natural intergenotypic recombinant RF1_2k/1b (RF1) strain.
  
  
  METHODS
  Genotyping and RF1-PCR screening were performed on samples from 604 HCV RNA-positive individuals from 7 countries. uPA/SCID mice carrying human hepatocytes (chimeric mice) were infected with the RF1_2k/1b strain, and the susceptibility of the strain to interferon and ribavirin was compared with the susceptibilities of 2 different strains of genotype B, used as references.
  
  
  RESULTS
  Six new RF1 cases were identified in this study; 5 (2%) of 281 in Russia and 1 (1%) of 90 in Uzbekistan. Phylogenetic analyses based on Core/E1 and NS5b indicated that all RF1 representatives share a common evolutionary ancestor. Infection with RF1 was established in chimeric mice. Reduction of RF1 viral load was observed in response to 3 injections of 3 microg/kg pegylated-interferon alpha-2a alone or in combination with 50 mg/kg of ribavirin (0.5 or 1.4 log-copies/mL).
  
  
  CONCLUSIONS
  All identified RF1-type strains appear to be introduced from a single source, suggesting that intergenotypic recombination in HCV is sporadic and not associated with cocirculation of different genotypes in a population. The RF1 strain in this study was responsive to interferon in vivo.
authors.affiliation: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Fuat
authors.initials: F
authors.lastname: Kurbanov
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Elena
authors.initials: E
authors.lastname: Chub
authors.forename: Isao
authors.initials: I
authors.lastname: Maruyama
authors.forename: Aziza
authors.initials: A
authors.lastname: Azlarova
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamitsukasa
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Ohno
authors.forename: Stefania
authors.initials: S
authors.lastname: Bonetto
authors.forename: Isabelle
authors.initials: I
authors.lastname: Moreau
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Fanning
authors.forename: Florence
authors.initials: F
authors.lastname: Legrand-Abravanel
authors.forename: Jaques
authors.initials: J
authors.lastname: Izopet
authors.forename: Nikolai
authors.initials: N
authors.lastname: Naoumov
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Sergei
authors.initials: S
authors.lastname: Netesov
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins; D011995:Recombination, Genetic; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a